text: For isotopes of elements like carbon and sulfur, the difference in kinetic parameters is too small, and the measurement precision too low, to measure an isotope effect by directly comparing the rates of the monoisotopic and rare isotope substrates. Instead, the two are mixed together using the natural abundance of stable isotopes in molecules. The enzyme is exposed to both isotopes simultaneously and its preference for the light isotope is analyzed by collecting the product of the reaction and measuring its isotope composition. For example, if an enzyme removes a carbon from a molecule by turning it into carbon dioxide, that carbon dioxide product can be collected and measured on an Isotope Ratio Mass Spectrometer for its carbon isotope composition. If the carbon dioxide has less C than the substrate mixture, the enzyme has preferentially reacted with the substrate that has a C at the site that is decarboxylated. In this way, internal competition experiments are also position-specific. If only the CO is measured, then only the isotope effect on the site of decarboxylation is recorded.